Cannabis extraction method and compositions

ABSTRACT

The present invention provides methods of extracting  Cannabis  plant material through use of  aloe , compositions comprising the resulting  Cannabis aloe  extracts, methods of using the extracts to ameliorate skin conditions, and applicators for applying the extracts topically.

This application claims benefit of priority to the filing date of U.S.provisional patent application 61/968,893, filed Mar. 21, 2014, thedisclosure of which is incorporated by reference herein.

FIELD OF THE INVENTION

The present invention pertains to methods of extracting materials frombiological sources, and particularly from plant matter for cosmetic andmedicinal applications.

BACKGROUND AND DESCRIPTION OF RELATED ART

Since the earliest days of mankind plants have been used as sources ofpharmacologically active materials. One such plant is Cannabis sativa,colloquially known as marijuana, which contains suchpharmacologically-active substances as Δ⁹-tetrahydrocannabinol and othercannabinoids, which historically were ingested by smoking dried leavesof Cannabis sativa.

For medical and cosmetic purposes use of crude plant material poses anumber of problems. First, it renders the dosage unknown and potentiallyhighly variable. Second, the pharmacologically-active material may wellconstitute only a small proportion of the plant in question. Third, thedesired pharmacologically-active material may well be admixed with toxicor otherwise undesirable adulterants. For this reason, it is oftendesirable to extract the desired pharmacologically-active material fromits biological source. Such considerations prompted, e.g., theextraction of salicylic acid from willow bark in the mid-eighteenthcentury, and to the extraction of taxol from the bark of the Pacific yewtree in the mid-twentieth century

U.S. Pat. No. 6,730,519 to Elsohly and Ross discloses a method ofextraction involving use of non-polar solvents and purification bycolumn chromatography on alumina columns.

US20030017216, filed by Schmidt and Coco, discloses an extraction methodthat uses various organic solvents but with a curtailed extractionperiod to extract primarily the surface structures of the plant.

U.S. Pat. No. 7,622,140 to Whittle et al. discloses an extraction methodthat uses hot air to volatilize cannabinoids.

U.S. Pat. No. 7,344,736 to Whittle et al. discloses an extraction methodthat uses sub-critical CO₂ to extract cannabinoids from Cannabis plantmaterial, while US20040049059, filed by Mueller and Mueller, discloses asupercritical CO₂ extraction method, as does. Similarly, US20080103193,filed by Castor et al., discloses use of super- or near-critical carbondioxide, nitrous oxide, ethylene, ethane, propane andchlorodifluoromethane, with or without organic co-solvents, asextractants for Cannabis plant material.

US20110256245, filed by Rosenblatt et al., discloses an extractionmethod for Cannabis flower trimmings with trichomes (glandular hairlikeappendages) involving covering the trimmings with cold water.

US20120264818, filed by Newland, discloses extraction of Cannabis plantmaterial with dimethylsulfoxide, and the use of the resulting extract asa topically applied composition for the treatment of various skinailments such as dermatitis.

U.S. Pat. No. 8,343,553, to Hospodor, discloses a device for preparingextracts of Cannabis plant material, as does US20130251824, filed byHospodor and Rapp.

US20130079531, filed by Barringer, discloses a process for rapidextraction of Cannabis plant material through brief contact with anorganic solvent below room temperature to minimize the extraction ofnon-cannabinoid contaminants.

U.S. Pat. No. 8,337,908, to Letzel et al., discloses use of Cannabisextracts for, inter alia, topical use in treatment of various skinailments, such extracts being prepared by a variety of known extractionmethods and extractants.

U.S. Pat. No. 8,603,515, to Whittle, discloses pharmaceuticalformulations of cannabinoids for administration via a pump action spray.

U.S. Pat. No. 8,512,767 to Ross discloses Cannabis-derived compositionssuitable for sublingual aerosol or spray delivery.

US20080119544, filed by Guy and Pertwee, discloses various therapeuticuses of cannabinoid extracts, as does US20080139667, filed by Robson andGuy. US20100249223, filed by Di Marzo et al., discloses the therapeuticand prophylactic use of cannabinoid extracts in connection with, interalia, cancer of the skin.

U.S. Pat. No. 8,524,286, to Smothers, discloses use of aloe to extractcardiac glycosides from Nerium oleander.

Each of the references above is hereby incorporated by reference in itsentirety.

While the possession or use of Cannabis has been illegal in the UnitedStates since 1937, the medicinal properties of cannabinoids (e.g., fortreatment of glaucoma) have become increasingly appreciated, which hasspurred efforts to facilitate the legal and controlled medical use ofcannabinoids. Extraction of cannabinoids and tetrahydrocannabinol fromCannabis plant material facilitates their use clinically by allowingadministration of compositions of known and/or predetermined potency andpurity. Accordingly, a need exists for a way to effectively extractpharmacologically-active compounds from plants of the genus Cannabis,and in particular using an extractant which itself is cosmeticallyacceptable or beneficial.

SUMMARY OF THE INVENTION

The present invention provides a method to extract cannabinoids such ascannabadiols and Δ⁹-tetrahydrocannabinols from plant material derivedfrom a plant of the genus Cannabis using aloe as extractant, such asthat derived from Aloe vera, to yield a Cannabis aloe extract. Theextract is useful for, inter alia, ameliorating skin conditions. Infurther embodiments, the invention provides pharmaceutical or cosmeticcompositions comprising the resulting Cannabis aloe extract, methods ofusing such compositions, and applicators comprising the extracts or thecompositions.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Definitions

Unless otherwise specified, technical terms take the meanings specifiedin the McGraw-Hill Dictionary of Scientific and Technical Terms, 6^(th)edition.

“Plant material” refers to any part of a plant, and includes bark, wood,leaves, stems, roots, flowers, fruits, seeds, berries as well asexudates, which optionally has been dried, cut into pieces, milled, orpowdered.

“Cannabis” refers to plants of the genus Cannabis. The genus includesCannabis sativa, (sometimes divided into the two subspecies Cannabisindica and Cannabis ruderalis), as well as all variants, chemovars, andsubspecies thereof, and also plants resulting from genetic crosses,self-crosses or hybrids thereof.

“Cannabis plant material” refers to plant material derived from a plantof the genus Cannabis. It includes Cannabis leaves and stems, whichpreferably may be cut into pieces, milled, dried, and/or powdered tofacilitate extraction.

“Aloe” refers to mucilage derived from a plant of the genus Aloe, whichincludes the species Aloe arborescens, Aloe aristata, Aloe dichotoma,Aloe nyeriensis, Aloe varvegata, Aloe wildii, and Aloe barbadensismiller among others, where “mucilage” here refers to the mucilageneousgel obtained from within the leaves of plants of the genus Aloe.Mucilage derived from an Aloe species, such as Aloe barbadensis miller,is obtained by methods well-known to those skilled in the art. Forexample, U.S. Pat. No. 4,957,907, which is hereby incorporated byreference in its entirety, describes in detail one procedure forproducing aloe. Aloe so obtained can be used either in liquid form, oras a powder (prepared, e.g., by freeze drying) that upon addition towater reconstitutes the liquid form.

“Cannabinoids” as used here refers to pharmacologically-active compoundsfound in plants of the genus Cannabis, most prominentlyΔ₉-tetrahydrocannabinol, Δ⁸-tetrahydrocannabinol, and cannabidiol, butalso including cannabinol and cannabigerol.

“Lower alkyl” refers to C₁-C₆ linear, branched, and alicyclichydrocarbons.

“Carrier” refers to a chemical compound, such as dimethylsulfoxide, thatfacilitates the incorporation of a compound into cells or tissues and/orprovides a vehicle for application of the extract, e.g. to skin.

“Diluent” refers to aqueous solutions of salts and buffers introduced toa composition to modify the pH and/or osmotic strength of thecomposition, one example of which is phosphate buffered saline.

“Dermal agents” refers to substances added to compositions to facilitatetheir topical application. Examples include ingredients used informulating cosmetics, such as an oily ointment, an aqueous ointment, acream, a lotion (e.g., a cosmetic lotion, a face lotion), an emulsion, apack, a soap, a face wash, a makeup (a body makeup, a face makeup), aspot cream, ointment or lotion, and combinations thereof.

“Skin condition” refers to various clinical pathologies and cosmeticmaladies of the skin, and includes abscesses, dry skin, sun-damagedskin, aging skin, acne, actinic keratosis, age spots, liver spots,burns, sunburn, heat burn, radiation burn, cold sores, corns, eczema,psoriasis, ringworm, scabies, skin cancers, basal skin cancer, squamousskin cancer, melanoma skin cancer, skin tags, and/or warts.

“Pharmaceutically acceptable carriers” refer to substances that arebiocompatible (i.e., not toxic to the host) and suitable for topicaladministration of a pharmacologically effective substance. Suitablepharmaceutically acceptable carriers include but are not limited tostabilizing agents, wetting and emulsifying agents, salts for varyingosmolarity, encapsulating agents, buffers, and skin penetrationenhancers. Examples of pharmaceutically acceptable carriers aredescribed in Remington's Pharmaceutical Sciences (Alfonso R. Gennaro,ed., 18th edition, 1990).

The compositions may comprise one or more pharmaceutically acceptablecarriers. Other ingredients well known in the art of preparing cosmeticsand other products suitable for application for the skin can be used aspharmaceutically acceptable carrier. Examples include lipophiliccompounds, such as glyceryl esters of a long-chain fatty acid (e.g.,glyceryl monostearate, glyceryl monopalmitate, myristyl laurate, andmyristyl palmitate), lanolin alcohol, palm oil, and other compoundsknown in the cosmetics art.

Extraction Method

In the process of the invention, Cannabis plant material is combinedwith an extractant which comprises, consists essentially of, or consistsof aloe, to form a Cannabis aloe extract.

The extraction method comprises mixing Cannabis plant material with aloein a ratio of about 1 to about 100 parts of aloe to one part of Cannabisplant material (w/w), and preferably 5-20 parts of aloe to one ofCannabis plant material (w/w), and most preferably about nine parts ofaloe to one part of Cannabis plant material (w/w), although the mosteffective proportions for extraction can be determined by the skilledartisan for any particular plant material or extractant.

The extraction mixture can optionally be heated to a temperature ofabout 40° C. to about 100° C., for about one to 10 hours, but neitherthe exact temperature nor the time is critical to the extraction, butmay enhance the degree of extraction. Similarly, the extraction mixturecan be agitated during extraction by, e.g., stirring, shaking,vortexing, sonicating, or other method, the choice of which is notcritical.

The extraction method can further optionally include use of additionalextractants such as lower alkyl alcohols, ketones, and esters which forman extraction mixture along with aloe. Examples of suitable additionalextractants include methanol, ethanol, propanol, n- and isopropanol,n-butanol, tert-butanol, acetone, methyl ethyl ketone, methoxyethanol,2-butoxyethanol, diethyl ether, acetone, butanone, and ethyl acetate.

The aloe extract of Cannabis aloe extract so obtained may be, andpreferably is, substantially separated from the remaining Cannabis plantmaterial by, for example, filtration, separation, centrifugation,screening (for example through a 1 or 0.5 micron screen), anddecantation or other separation methods including the use of filterscreens, mesh, or fibrous materials or other man-made or materials foundin nature the choice of which is not critical, of porous nature fromvarious types of rock, sand, clay or charcoal type materials tofacilitate the further separation of plant components, as known in theart. In addition, various lipids can optionally be removed from theCannabis aloe extract by processes such as “winterization”, viz.,chilling (e.g., to −20° C.) followed by filtration to remove waxyballast.

The Cannabis aloe extract is normally recovered as a liquid but may beconverted and maintained for storage as a solid (e.g. freeze dried)which can be reconstituted to a liquid, for example by adding water.

For some purposes it may be desirable to produce Cannabis aloe extractswith differing proportions of the constituent cannabinoids. For example,in some contexts it may be desirable to have a higher proportion ofcannabadiol than Δ⁹-tetrahydrocannabinol than in others. Suchmanipulation of the relative proportions of the various cannabinoids canbe readily effected by changes in the extractant(s) or extractionconditions, and/or choice of particular Cannabis cultivars chosen forthe relative proportions of cannabinoids they contain.

Pharmaceutical Compositions

Cannabis aloe extracts obtained as described above provide a basis forpharmaceutical compositions that comprise the Cannabis aloe extract andat least one pharmaceutically acceptable carrier. Another embodimentprovides cosmetic compositions comprising a Cannabis aloe extract and atleast one dermal agent.

The term “pharmaceutical composition” as used here refers to Cannabisaloe extract in combination with other chemical components, such asdiluents, carriers, excipients and auxiliaries to facilitate topicalapplication of the Cannabis aloe extract to an organism. The term“pharmaceutical composition” as used here includes cosmetic compositionsand food or nutraceutical compositions, which are not necessarilyintended for use in the treatment of a particular skin pathology. Theinventive pharmaceutical compositions can be administered to the skin inthe form of an ointment, a poultice, a plaster, a compress, a balm, anunguent, a salve, an emollient, and other forms suitable foradministering substances to the skin.

Further, the inventive pharmaceutical composition can also be formulatedfor routes of administration other than topical. In some context, forexample, it may be desirable to administer compositions based onCannabis aloe extracts orally, sublingually, buccally, vaginally, orrectally, for which purpose suitable formulations can be prepared, withdiluents, carriers, excipients and auxiliaries selected for thecontemplated route of administration. As such, the present inventioncontemplates tablets, capsules, liquid gels, suppositories, and otherwell-known dosage forms as vehicles for administration of pharmaceuticalcompositions comprising Cannabis aloe extracts.

Techniques for formulating and administrating the pharmaceuticalcompositions may be found in “Remington's Pharmaceutical Sciences,” MackPublishing Co., Easton, Pa., 18th edition, 1990.

The pharmaceutical compositions described herein can be administered toa human patient per se, or as part of other pharmaceutical compositionswhere they are mixed with other active ingredients, as in combinationtherapy, or suitable carriers or excipient(s).

Methods of Treatment

This application also discloses a method of treating or otherwiseameliorating a skin condition (as defined above) comprising applying anefficacious amount of the inventive pharmaceutical composition to theskin of a subject. In this context, treating a skin condition does notnecessarily imply medical treatment, and thus for example may includeproviding a benefit typically associated with the application of acosmetic, such as soothing, softening or moisturizing the skin,facilitating the toning, and tightening of skin, reduction of pore sizeand reduction of appearance of blemishes, spots and wrinkles, and/orhair.

In practice an efficacious amount of the pharmaceutical compositionmeans applying Cannabis aloe extract containing sufficient cannabinoidsto prevent, alleviate or ameliorate symptoms of disease in the subjectbeing treated. Determination of what constitutes an efficacious amountis within the capability of those skilled in the art, and may involveassaying a given portion of Cannabis aloe extract for its cannabinoidcontent.

Methods of assaying cannabinoids, especially through immunologicalmethods, are well-known in the literature, and allow ready determinationof the cannabinoid concentration in a Cannabis aloe extract sample. U.S.Pat. No. 5,747,352, to Yan et al., U.S. Pat. No. 5,910,419, to Johnsonet al., U.S. Pat. No. 6,720,192 to Viel and Ensing, U.S. Pat. No.7,749,712, to Pull et al., and U.S. Pat. No. 8,518,653, to Takkinen etal., each of which is hereby incorporated by reference in its entirety,each describe methods of determining the amount and relative proportionof cannabinoids in a given sample.

The amount of the inventive pharmaceutical composition administered willgenerally be dependent on the subject being treated, on the subject'sweight, the nature and severity of the skin condition, the manner ofadministration, the concentration and identity of the cannabinoids inthe Cannabis aloe extract, and the judgment of the prescribingphysician.

Applicator

Further embodiments of the invention provide an applicator to be used inconjunction with the Cannabis aloe extracts or pharmaceuticalcompositions, wherein the applicator contains the extract or thepharmaceutical composition and is used to apply it to the skin of asubject. The applicator can take the form of a hand-actuated pump, anaerosol can, a patch, or a rollon device such as those used forapplication of deodorants.

EXAMPLES Example 1

Dried leaves and stems of Cannabis sativa (100 g) were milled to a finepowder, weighed into a glass container and mixed with aloe derived fromAloe barbadensis leaf juice (900 g) that had been processed to a liquidwith a maximum anthraquinone (aloin and/or aloe emodin) content of 1ppm, pH of 3.7-4.1, and containing 0.1% potassium sorbate.

The resulting extraction mixture was agitated until homogeneous, and thecontainer with the extraction mixture was placed into a temperaturecontrolled water bath at 80-85° C. for five hours with no agitation. Theconditioned extraction mixture was then covered and allowed to cool.

After the extraction mixture cooled, a portion of the mixture wasseparated from the residual plant material by decantation. The extractwas then separated from any remaining plant material by straining. Theextract was then agitated until homogeneous.

The extract was then filtered through a medium of approximately 1 micronporosity, followed by a second filtration through a medium of 0.5-1.0micron porosity, and the resulting extract (substantially free of plantmaterial) was stored in a sealed glass container at ambient temperature.

Example 2

An extract (substantially free of residual plant material) prepared asdescribed in Example 1 was combined with a dermal agent in a ratio of 4parts by weight of extract to 1 part by weight of dermal agent, based onthe total weight of the pharmaceutical composition. The dermal agentcontained Glycerin, Methyl Sulfonyl Methane, Oryzo Sativa (Rice Bran)Oil, Ricinus Communis (Castor) Oil, glyceryl stearate, styrene/acrylatescopolymer, PEG-100 stearate, cetyl alcohol, dimethicone, carbomer,caprylyl glycol, glycerin, glyceryl caprylate, phenylpropanol, methylparaben, tocopherol (vitamin E), and fragrance.

Those of skill in the art will appreciate that numerous and variousmodifications can be made without departing from the spirit of thepresent invention. The various embodiments of the present inventiondescribed herein are illustrative only and not intended to limit thescope of the present invention.

1. A method of preparing Cannabis aloe extract, comprising mixingCannabis plant material with an extractant comprising aloe, therebyforming a Cannabis aloe extract.
 2. The method of claim 1, furthercomprising separating the Cannabis plant material from the Cannabis aloeextract to recover a Cannabis aloe extract substantially free ofCannabis plant material.
 3. The method of claim 1, wherein the Cannabisplant material is derived from a species selected from the groupconsisting of Cannabis sativa, Cannabis indica, and Cannabis ruderalis.4. The method of claim 1, wherein the Cannabis plant material is derivedfrom Cannabis sativa.
 5. The method of claim 1, wherein about one partto about 50 parts by weight of Cannabis plant material is mixed withabout one part to about 100 parts by weight of aloe.
 6. The method ofclaim 1, wherein the extraction mixture optionally further comprises aleast one additional extractant selected from the group consisting ofalcohols, ketones, and esters.
 7. The method of claim 6, wherein theadditional extractant is selected from the group consisting of methanol,ethanol, propanol, n- and iso-propanol, n-butanol, tert-butanol,acetone, methyl ethyl ketone, methoxyethanol, 2-butoxyethanol, diethylether, acetone, butanone, and ethyl acetate, and mixtures thereof. 8.The method of claim 1, wherein the separating method is selected fromthe group consisting of filtration, centrifugation, and decanting orcombinations thereof.
 9. The method of claim 1, further comprisingheating the mixture from about 25° C. to about 100° C., for a periodbetween about 1 hour and about 10 hours.
 10. A Cannabis aloe extractprepared as claimed in claim
 1. 11. A pharmaceutical composition,comprising the Cannabis aloe extract of claim 10 and at least onepharmaceutically acceptable carrier.
 12. A cosmetic compositioncomprising the Cannabis aloe extract of claim 10 and at least one dermalagent.
 13. A method of treating a skin condition in a patient in needthereof, comprising applying an effective amount of the pharmaceuticalcomposition of claim 11 to the skin of the patient.
 14. The method oftreatment of claim 13 wherein the skin condition is selected from thegroup consisting of abscesses, dry skin, sun-damaged skin, aging skin,acne, actinic keratosis, age spots, liver spots, burns, sunburn, heatburn, radiation burn, cold sores, corns, eczema, psoriasis, ringworm,scabies, skin cancers, basal skin cancer, squamous skin cancer, melanomaskin cancer, skin tags, and warts.
 15. A method of cosmetically treatingskin, comprising identifying a subject in need of cosmetic application,and applying a cosmetically effective amount of the cosmetic compositionof claim 12 to the skin of the subject.
 16. An applicator devicecontaining Cannabis aloe extract of claim
 10. 17. The applicator ofclaim 16, wherein the applicator is selected from the group consistingof a hand-actuated pump, an aerosol can, a patch, and a roll-on device.18. An applicator device containing the cosmetic composition of claim12.